We intend to map the cyclic pathways involving pyruvate in hepatocytes and kidney cortex tubules. Effects of changes in diet and of chronic and acute hormonal treatment will be studied. The effects of glucagon and epinephrine on gluconeogenesis and cycling through pyruvate kinase will be compared. Also we will study the effects of adrentlectomy on pyruvate cycling, and of triiodothyronine treatment on futile hydrogen, cycling between mitochondria and cytosol. The fluxes in the intact cell will be mapped using a number of specifically 14C labelled metabolites, with the use of a steady state model and a microcomputer. Stepwise degradation of the main products (glucose, lactate, glutamate, etc.) and key intermediates permit a quantitative outline of metabolism. Key rate-limiting steps will be pinpointed by a new inhibitor titration technique, and the mechanism of hormonal action at these sites will be studied.